Erythromycin regulates peroxisome proliferator-activated receptor γ to ameliorate cigarette smoke-induced oxidative stress in macrophages.

Background: Chronic obstructive pulmonary disease (COPD) is significantly influenced by oxidative stress. Recent studies have elucidated the anti-oxidative stress properties of peroxisome proliferator-activated receptors γ (PPARγ), augmenting its known anti-inflammatory effects. The exact influence of PPARγ on oxidative stress in COPD remains elusive. This study aimed to investigate the potential mechanism by which PPARγ counteracts the oxidative stress instigated by cigarette smoke in macrophages. Methods: Macrophages were cultured and exposed to 1% cigarette smoke extract (CSE), 1 µg/mL erythromycin (EM), and 10 µmol/mL GW9662 (a PPARγ antagonist). Reactive oxygen species (ROS) in macrophages was identified using fluorescent microscopy. PPARγ expression was ascertained through reverse transcription-polymerase chain reaction (RT-PCR) and Western blot techniques. The superoxide dismutase (SOD) in macrophage supernatant was measured by enzyme linked immunosorbent assay (ELISA), as was malondialdehyde (MDA). Results: Our results shown that cigarette smoke stimulated macrophages to increase ROS release, decrease the expression of PPARγ, increase the expression of MDA and decrease the expression of SOD. After PPARγ inhibitor acted on macrophages stimulated by cigarette smoke, the expression of MDA was inhibited and the content of SOD increased. When EM was used to treat macrophages stimulated by cigarette smoke, the expression of ROS decreased, the expression of PPARγ increased, the expression of MDA decreased and the expression of SOD increased. Conclusions: This study suggests that PPARγ plays an anti-oxidative role by inhibiting the expression of MDA and promoting the expression of SOD. Cigarette smoke induces oxidative stress by inhibiting PPARγ pathway. EM inhibits oxidative stress by activating PPARγ pathway.

Innate immune responsive inflammation in development of progressive myopia.

PURPOSE: Inflammation has been implicated for development of myopia. It is not clear when inflammation is kicked in during the course of myopia, and what characteristics of the inflammation. In this study, we tested for cytokines from aqueous humour of eyes with wide spectrum of refractive status for profiling the inflammation. METHODS: Aqueous humour of 142 patient eyes were tested for soluble intercellular adhesion molecule 1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta 2 (TGF-ß2) using an enzyme-linked immunosorbent assay (ELISA). Eye globe axial length of these patients ranged from emmetropia to high myopia. RESULTS: Of 142 patients, an average axial length is 25.51 ± 3.31 mm, with a range of 21.56-34.37 mm. There are 36 cases in lower 25 percentile, 37 cases in upper 25 percentile, and 69 case in the middle 50 percentile. sICAM-1 and MCP-1 were significantly higher in the eyes with staphyloma (407.48 pg/mL, 312.31 pg/mL, n = 33) or macular schisis (445.86 pg/mL,345.33 pg/mL, n = 19) than that in the eyes without these changes (206.44 pg/mL, 244.76 pg/mL, n = 107). All three cytokines level was significantly associated with eye globe axial in a positive mode while adjusting for the age and sex. Strength of the association was the greatest for sICAM-1 and the weakest for TGF- ß2. MCP-1 was in between. CONCLUSION: sICAM-1 and MCP-1 in ocular fluid may be indicative biomarkers for progressive high myopia and the underneath autoimmune inflammation. sICAM-1 may be used as a monitoring biomarker for development of pathologic myopia.

ARTIFICIAL INTELLIGENCE FOR OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY-BASED DISEASE ACTIVITY PREDICTION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The authors hypothesize that optical coherence tomography angiography (OCTA)-visualized vascular morphology may be a predictor of choroidal neovascularization status in age-related macular degeneration (AMD). The authors thus evaluated the use of artificial intelligence (AI) to predict different stages of AMD disease based on OCTA en face 2D projections scans. METHODS: Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active, and wet AMD in remission with no signs of activity. Two human experts graded the same test set, and a consensus grading between two experts was used for the prediction of four categories. RESULTS: The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and the specificity was 0.9524, 0.9524, 0.9286, and 0.9524, respectively. The sensitivity of prediction by human experts was 0.4286 active choroidal neovascularization, 0.2143 remission, 0.8571 dry AMD, and 0.8571 normal with specificity of 0.7619, 0.9286, 0.7857, and 0.9762, respectively. The overall AI classification prediction was significantly better than the human (odds ratio = 1.95, P = 0.0021). CONCLUSION: These data show that choroidal neovascularization morphology can be used to predict disease activity by AI; longitudinal studies are needed to better understand the evolution of choroidal neovascularization and features that predict reactivation. Future studies will be able to evaluate the additional predicative value of OCTA on top of other imaging characteristics (i.e., fluid location on OCT B scans) to help predict response to treatment.

Ultra-wide field and new wide field composite retinal image registration with AI-enabled pipeline and 3D distortion correction algorithm.

PURPOSE: This study aimed to compare a new Artificial Intelligence (AI) method to conventional mathematical warping in accurately overlaying peripheral retinal vessels from two different imaging devices: confocal scanning laser ophthalmoscope (cSLO) wide-field images and SLO ultra-wide field images. METHODS: Images were captured using the Heidelberg Spectralis 55-degree field-of-view and Optos ultra-wide field. The conventional mathematical warping was performed using Random Sample Consensus-Sample and Consensus sets (RANSAC-SC). This was compared to an AI alignment algorithm based on a one-way forward registration procedure consisting of full Convolutional Neural Networks (CNNs) with Outlier Rejection (OR CNN), as well as an iterative 3D camera pose optimization process (OR CNN + Distortion Correction [DC]). Images were provided in a checkerboard pattern, and peripheral vessels were graded in four quadrants based on alignment to the adjacent box. RESULTS: A total of 660 boxes were analysed from 55 eyes. Dice scores were compared between the three methods (RANSAC-SC/OR CNN/OR CNN + DC): 0.3341/0.4665/4784 for fold 1-2 and 0.3315/0.4494/4596 for fold 2-1 in composite images. The images composed using the OR CNN + DC have a median rating of 4 (out of 5) versus 2 using RANSAC-SC. The odds of getting a higher grading level are 4.8 times higher using our OR CNN + DC than RANSAC-SC (p < 0.0001). CONCLUSION: Peripheral retinal vessel alignment performed better using our AI algorithm than RANSAC-SC. This may help improve co-localizing retinal anatomy and pathology with our algorithm.

Prevalence, Characteristics, and Treatment of Hemorrhoids During Pregnancy: A Nationwide Population-Based Cohort Study in Taiwan.

Background: Hemorrhoids, a gastrointestinal tract disorder, are common during pregnancy. However, large-scale epidemiological studies on hemorrhoids during pregnancy are limited. Therefore, this study used analyzed data from a nationwide population-based database to investigate the prevalence, characteristics, and treatment of hemorrhoids in Taiwan. Materials and Methods: This retrospective population-based study used data from the National Health Insurance Research Database and Taiwan Birth Certificate Application to collect the medical records of women who were pregnant at any time during 2009-2018. Hemorrhoids was defined by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) (455. X) and International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) (K64.X, O22.4X) with related treatment. Results: We enrolled 1,608,804 deliveries in 1,070,708 women. The proportion of hemorrhoids increased with age in both primipara and multipara women. Of the pregnant women, 31% received oral medication, and 93.2% used the topical ointment to treat their hemorrhoids. Few patients (1.8%) required procedure or surgery during pregnancy, and 41.4% of those patients underwent procedure or surgery in their first trimester. The cumulative incidence of hemorrhoids during pregnancy was significantly higher in women with a history of hemorrhoids and those with multifetal pregnancies. No significant difference in the incidence of hemorrhoids was observed between multiparous and primiparous women. Conclusion: Women with a history of hemorrhoids or those carrying multiple fetuses had an increased risk of hemorrhoids during pregnancy. The most commonly used treatment for hemorrhoids during pregnancy was topical ointments, with only a small proportion (1.8%) of patients requiring procedure or surgery.

Phosphorus partitioning contribute to phosphorus use efficiency during grain filling in Zea mays.

Introduction: Lower phosphorus (P) availability limits crop productivity in agroecosystems. The remobilization of P from the source to the sink organs plays an important role in enhancing the P-utilization efficiency of crops. During the grain filling stage, phosphorus flow to the developing grains, the primary sink, determines crop yield. However, the specific contributions of different organs to grain P throughout the post-silking period in maize remain unclear. Methods: In our study, three maize inbred lines (CIMBL89, Ji846, and CML118) with contrasting P statuses were selected and grown in a field with high P (HP, 150 kg ha-1 P2O5) and low P (LP, 0 kg ha-1 P2O5) conditions. Results: The grain yield of CIMBL89 was 69% and 169% greater under HP supply, and 83% and 309% greater than those of Ji846 and CML118 under LP supply, respectively. The ear length, ear diameter, and kernel row number of CML118 were lower than those of CIMBL89 and Ji846 under HP conditions. Most of the P (87%) in the grains of CIMBL89 came from P uptake at the LP supply, while almost all P (95%) came from P remobilization in various organs at the HP supply after silking. In contrast, 91% of the P found in the grain of CML118 came from P remobilization under LP supply, while 76% came from P uptake under HP supply after silking. Discussion: In conclusion, our findings suggest that CIMBL89, with greater P acquisition efficiency, contributes to grain formation and production during the post-silking period under LP conditions. Additionally, CIMBL89 can fully remobilize P and avoid the extravagant absorption of P in P-sufficient soil, which sets it apart from Ji846 and CML118.

Retinal tissue and microvasculature loss in COVID-19 infection.

This cross-sectional study aimed to investigate the hypothesis that permanent capillary damage may underlie the long-term COVID-19 sequela by quantifying the retinal vessel integrity. Participants were divided into three subgroups; Normal controls who had not been affected by COVID-19, mild COVID-19 cases who received out-patient care, and severe COVID-19 cases requiring intensive care unit (ICU) admission and respiratory support. Patients with systemic conditions that may affect the retinal vasculature before the diagnosis of COVID-19 infection were excluded. Participants underwent comprehensive ophthalmologic examination and retinal imaging obtained from Spectral-Domain Optical Coherence Tomography (SD-OCT), and vessel density using OCT Angiography. Sixty-one eyes from 31 individuals were studied. Retinal volume was significantly decreased in the outer 3 mm of the macula in the severe COVID-19 group (p = 0.02). Total retinal vessel density was significantly lower in the severe COVID-19 group compared to the normal and mild COVID-19 groups (p = 0.004 and 0.0057, respectively). The intermediate and deep capillary plexuses in the severe COVID-19 group were significantly lower compared to other groups (p < 0.05). Retinal tissue and microvascular loss may be a biomarker of COVID-19 severity. Further monitoring of the retina in COVID-19-recovered patients may help further understand the COVID-19 sequela.

DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR.

PURPOSE: To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting. METHODS: Retrospective review of secondary MH surgeries. RESULTS: A total of 72 eyes from 72 patients were included. Eyes had a mean of 1.51 surgeries before inclusion into this study with a mean MH size of 762 µ m and a mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.11 (∼20/260 Snellen). Closure rates were 89.3% for tissue transplantation, 77.3% for internal limiting membrane (ILM) flaps, 92.9% for MH manipulation, and 12.5% for repeat ILM peeling ( P < 0.05). Best-corrected visual acuity changes in logarithm of the minimum angle of resolution from baseline to postoperative month six were +0.29 for ILM peeling alone (15 Early Treatment Diabetic Retinopathy Study letters worse), -0.39 for MH manipulation (20 Early Treatment Diabetic Retinopathy Study letters improved), -0.23 for tissue transplantation (13 Early Treatment Diabetic Retinopathy Study letters improved), and -0.2 for ILM flaps (10 Early Treatment Diabetic Retinopathy Study letters improved; P < 0.05). CONCLUSION: Secondary MH closure is possible using various surgical techniques with acceptable anatomical closure rates. Repeat ILM peeling is associated with the lowest closure rates and poorest functional results. To distinguish between techniques would require a large sample size of approximately 750 eyes.

Biomechanical Considerations of Patching Material for Posterior Scleral Reinforcement Surgery.

Purpose: To characterize biomechanical properties of genipin-crosslinked human dura mater as reinforcing material for posterior scleral reinforcement (PSR) and to compare it with crosslinked human sclera. Methods: Donor dura mater and sclera were crosslinked in the same optimized genipin solution. Resistance to enzyme degradation for both materials were investigated by exposing the materials to accelerated enzyme degrading. Elastic modulus and tensile strength were measured by biomechanics testing equipment. Crosslinked human dura mater was used as reinforcing patch in PSR on 57 adult pathologic myopic eyes. The patients were followed up for an average 3 years. The main outcome was eye globe axial length change and safety profile of the reinforcing material. Results: Crosslinked dura mater demonstrated similar percentage weight loss to crosslinked sclera when exposed to enzymatic solution. Dura mater has higher density than sclera. The retaining elastic modulus after enzyme exposure was 72.02 MPa for crosslinked dura mater while 53.88 MPa for crosslinked sclera, 34% greater for crosslinked dura mater, P = 0.0186). At the end of 3 years follow-up, the mean globe axis of the surgery eyes was reduced by 1.29 mm (from 30.81 to 29.51 mm, P < 0.0001, paired t-test). Visual acuity (BCVA logMar) improved by 0.10 logMar unit which is an improvement of five letters (P = 0.0184, paired t-test). No material specific complication was noted. Conclusion: Crosslinked human dura mater may be superior to crosslinked human sclera as reinforcing material for PSR to manage progression of high myopia. This material was well tolerated on human eye.

Effect of Thermoelectric Warming Therapy for the Treatment of Meibomian Gland Dysfunction.

PURPOSE: To evaluate the efficacy of thermoelectric warming therapy (MiBoFlo) in improving patient symptoms with standardized questionnaires and objective signs of meibomian gland dysfunction (MGD), which is an important underlying treatable factor in dry eye disease (DED), such as ocular surface staining, tear quality, and meibomian gland morphology. Multivariate analysis to identify predictors for the improvement in Ocular Surface Disease Index (OSDI) was also performed. DESIGN: Retrospective before-and-after study. METHODS: A total of 203 eyes of 102 patients with DED were treated with MiBoFlo at the dry eye center. The OSDI and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires, best-corrected visual acuity, tear osmolarity, tear film breakup time (TBUT), corneal and conjunctival staining, meibography, number of glands expressing liquid, and quality of the improved meibum were assessed before and 6 months after MiBoFlo. Exclusion criteria included active ocular inflammation. RESULTS: Dry eye symptoms improved in the population, with both SPEED and OSDI lowering of dry eye symptoms by approximately 35% (P < .001) at month 6. Significant improvements in lissamine green conjunctival staining, corneal fluorescein staining, TBUT, osmolarity, and secreting meibomian glands and meibum quality were also seen. Improvement was seen across all domains of the questionnaires and across all baseline parameters. Eyes with blepharitis and autoimmune disease improved less than average. No complications or adverse events occurred. CONCLUSIONS: MiBoFlo treatments produced clinical and statistically significant improvements in the signs and symptoms of MGD, irrespective of underlying ocular conditions. This improvement was sustained for the 6-month period of observation after initiating the treatment.

Ensuring future food security and resource sustainability: insights into the rhizosphere.

Feeding the world's growing population requires continuously increasing crop yields with less fertilizers and agrochemicals on limited land. Focusing on plant belowground traits, especially root-soil-microbe interactions, holds a great promise for overcoming this challenge. The belowground root-soil-microbe interactions are complex and involve a range of physical, chemical, and biological processes that influence nutrient-use efficiency, plant growth and health. Understanding, predicting, and manipulating these rhizosphere processes will enable us to harness the relevant interactions to improve plant productivity and nutrient-use efficiency. Here, we review the recent progress and challenges in root-soil-microbe interactions. We also highlight how root-soil-microbe interactions could be manipulated to ensure food security and resource sustainability in a changing global climate, with an emphasis on reducing our dependence on fertilizers and agrochemicals.

Combining analyses of metabolite profiles and phosphorus fractions to explore high phosphorus utilization efficiency in maize.

Phosphorus (P) limitation is a significant factor restricting crop production in agricultural systems, and enhancing the internal P utilization efficiency (PUE) of crops plays an important role in ensuring sustainable P use in agriculture. To better understand how P is remobilized to affect crop growth, we first screened P-efficient (B73 and GEMS50) and P-inefficient (Liao5114) maize genotypes at the same shoot P content, and then analyzed P pools and performed non-targeted metabolomic analyses to explore changes in cellular P fractions and metabolites in maize genotypes with contrasting PUE. We show that lipid P and nucleic acid P concentrations were significantly lower in lower leaves of P-efficient genotypes, and these P pools were remobilized to a major extent in P-efficient genotypes. Broad metabolic alterations were evident in leaves of P-efficient maize genotypes, particularly affecting products of phospholipid turnover and phosphorylated compounds, and the shikimate biosynthesis pathway. Taken together, our results suggest that P-efficient genotypes have a high capacity to remobilize lipid P and nucleic acid P and promote the shikimate pathway towards efficient P utilization in maize.

Enhanced Oral NO Delivery through Bioinorganic Engineering of Acid-Sensitive Prodrug into a Transformer-like DNIC@MOF Microrod.

Nitric oxide (NO) is an endogenous gasotransmitter regulating alternative physiological processes in the cardiovascular system. To achieve translational application of NO, continued efforts are made on the development of orally active NO prodrugs for long-term treatment of chronic cardiovascular diseases. Herein, immobilization of NO-delivery [Fe2(µ-SCH2CH2COOH)2(NO)4] (DNIC-2) onto MIL-88B, a metal-organic framework (MOF) consisting of biocompatible Fe3+ and 1,4-benzenedicarboxylate (BDC), was performed to prepare a DNIC@MOF microrod for enhanced oral delivery of NO. In simulated gastric fluid, protonation of the BDC linker in DNIC@MOF initiates its transformation into a DNIC@tMOF microrod, which consisted of DNIC-2 well dispersed and confined within the BDC-based framework. Moreover, subsequent deprotonation of the BDC-based framework in DNIC@tMOF under simulated intestinal conditions promotes the release of DNIC-2 and NO. Of importance, this discovery of transformer-like DNIC@MOF provides a parallel insight into its stepwise transformation into DNIC@tMOF in the stomach followed by subsequent conversion into molecular DNIC-2 in the small intestine and release of NO in the bloodstream of mice. In comparison with acid-sensitive DNIC-2, oral administration of DNIC@MOF results in a 2.2-fold increase in the oral bioavailability of NO to 65.7% in mice and an effective reduction of systolic blood pressure (SBP) to a ΔSBP of 60.9 ± 4.7 mmHg in spontaneously hypertensive rats for 12 h.

Mechanisms for improving phosphorus utilization efficiency in plants.

BACKGROUND: Limitation of plant productivity by phosphorus (P) supply is widespread and will probably increase in the future. Relatively large amounts of P fertilizer are applied to sustain crop growth and development and to achieve high yields. However, with increasing P application, plant P efficiency generally declines, which results in greater losses of P to the environment with detrimental consequences for ecosystems. SCOPE: A strategy for reducing P input and environmental losses while maintaining or increasing plant performance is the development of crops that take up P effectively from the soil (P acquisition efficiency) or promote productivity per unit of P taken up (P utilization efficiency). In this review, we describe current research on P metabolism and transport and its relevance for improving P utilization efficiency. CONCLUSIONS: Enhanced P utilization efficiency can be achieved by optimal partitioning of cellular P and distributing P effectively between tissues, allowing maximum growth and biomass of harvestable plant parts. Knowledge of the mechanisms involved could help design and breed crops with greater P utilization efficiency.

Flavonoids are involved in phosphorus-deficiency-induced cluster-root formation in white lupin.

BACKGROUND AND AIMS: Initiation of cluster roots in white lupin (Lupinus albus) under phosphorus (P) deficiency requires auxin signalling, whereas flavonoids inhibit auxin transport. However, little information is available about the interactions between P deficiency and flavonoids in terms of cluster-root formation in white lupin. METHODS: Hydroponic and aeroponic systems were used to investigate the role of flavonoids in cluster-root formation, with or without 75 µm P supply. KEY RESULTS: Phosphorus-deficiency-induced flavonoid accumulation in cluster roots depended on developmental stage, based on in situ determination of fluorescence of flavonoids and flavonoid concentration. LaCHS8, which codes for a chalcone synthase isoform, was highly expressed in cluster roots, and silencing LaCHS8 reduced flavonoid production and rootlet density. Exogenous flavonoids suppressed cluster-root formation. Tissue-specific distribution of flavonoids in roots was altered by P deficiency, suggesting that P deficiency induced flavonoid accumulation, thus fine-tuning the effect of flavonoids on cluster-root formation. Furthermore, naringenin inhibited expression of an auxin-responsive DR5:GUS marker, suggesting an interaction of flavonoids and auxin in regulating cluster-root formation. CONCLUSIONS: Phosphorus deficiency triggered cluster-root formation through the regulation of flavonoid distribution, which fine-tuned an auxin response in the early stages of cluster-root development. These findings provide valuable insights into the mechanisms of cluster-root formation under P deficiency.

Levonorgestrel intrauterine system for the treatment of intermenstrual spotting in patients with previous cesarean delivery scar defect.

AIM: To evaluate the efficacy of levonorgestrel 52 mg intrauterine system for intermenstrual bleeding in patients with previous cesarean delivery scar defects (PCDSs). METHODS: The medical records of 28 consecutive patients with previous cesarean delivery scar defect and intermenstrual bleeding who had undergone conservative treatment with levonorgestrel 52 mg intrauterine system were reviewed. The efficacy of treatment and frequency of adverse events were measured retrospectively. RESULTS: After 1 year of treatment, 22 patients (78.6%) reported an improvement in symptoms. The mean duration of menstruation were 18 and 5 days before and after treatment, respectively. No uterine perforations or pelvic inflammatory diseases occurred during or after the insertion procedures. Eighteen (64.3%) patients did not experience any adverse events, and the patients with adverse events reported that they could be managed by adjusting their medications or observation. CONCLUSION: Levonorgestrel intrauterine system may have a role in the safe and effective management of intermenstrual spotting in patients with PCDSs.

Effective treatment of retinal neovascular leakage with fusogenic porous silicon nanoparticles delivering VEGF-siRNA.

Aim: To evaluate an intravitreally injected nanoparticle platform designed to deliver VEGF-A siRNA to inhibit retinal neovascular leakage as a new treatment for proliferative diabetic retinopathy and diabetic macular edema. Materials & methods: Fusogenic lipid-coated porous silicon nanoparticles loaded with VEGF-A siRNA, and pendant neovascular integrin-homing iRGD, were evaluated for efficacy by intravitreal injection in a rabbit model of retinal neovascularization. Results: For 12 weeks post-treatment, a reduction in vascular leakage was observed for treated diseased eyes versus control eyes (p = 0.0137), with a corresponding reduction in vitreous VEGF-A. Conclusion: Fusogenic lipid-coated porous silicon nanoparticles siRNA delivery provides persistent knockdown of VEGF-A and reduced leakage in a rabbit model of retinal neovascularization as a potential new intraocular therapeutic.

Changes of plasma nitric oxide, endothelin-1, and blood coagulation following intravitreal conbercept.

Intravitreal anti-VEGF (anti-vascular endothelial growth factor) biologics have revolutionized the pharmacological management of chorioretinal diseases. However, the systemic adverse events such as stroke or bleeding are the concerns for many patients and physicians. The mechanism to develop these side effects are poorly understood. Consecutive 95 patients with retinal diseases were studied for their blood activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), and concentration of fibrinogen before and after intravitreal conbercept. Additionally, plasma nitric oxide (NO) and endothelin-1 (ET-1) were investigated on 38 of the 95 patients. Compared with the pre-injection, 4-week post-injection values of APTT and PT were increased by 0.582 s (p = 0.038, paired t test) and by 0.086 s (p = 0.080, paired t test; p = 0.0475, Sign test), respectively. At the same time, fibrinogen decreased by 0.048 g/L. Plasma levels of NO or ET-1 or VEGF did not significantly change from pre-injection levels. Our findings advanced the understanding of mechanism for systemic side effects associated with intravitreal anti-VEGF and emphasized paying more attention to higher risk of possible bleedings for patients following intravitreal conbercept.

CHOROIDAL IMAGING BIOMARKERS TO PREDICT HIGHLY RESPONSIVE AND RESISTANT CASES TREATED WITH STANDARDIZED ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR REGIMEN IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine structural predictors of treatment response in neovascular age-related macular degeneration analyzing optical coherence tomography (OCT)-related biomarkers. METHODS: A retrospective review of patients undergoing treatment for neovascular age-related macular degeneration at a tertiary institute was performed at presentation. High-intensity regimen included eyes on long-term anti-vascular endothelial growth factor treatment with the inability to extend beyond a month without a relapse and needed double the dose of medication (n = 25). Low-intensity regimen had eyes that went into long-term remission after at least three injections and remained dry for more than a year until the last visit (n = 20). Multimodal imaging including fluorescein angiogram, OCT, and comprehensive ocular evaluation were done. Choroidal vascularity index, total choroidal area, luminal area, subfoveal choroidal thickness, choriocapillaris thickness and Haller and Sattler layer thickness were analyzed for statistical significance. RESULTS: The groups had no significant difference at baseline in age, gender, incidence of reticular pseudodrusen, polypoidal choroidal vasculopathy feature on OCT, type of choroidal neovascular membrane, and geographic atrophy. Multinomial logistic regression revealed that thicker subfoveal choroidal thickness and larger total choroidal area were the significant predictors of poor response to anti-vascular endothelial growth factor treatment (E = 0.02; P = 0.02; E = 1.82; P = 0.0075). CONCLUSION: Thicker subfoveal choroidal thickness and higher total choroidal area are useful variables to predict a poor treatment response.

Controlled release of triamcinolone from an episcleral micro film delivery system for open-globe eye injuries and proliferative vitreoretinopathy.

Open globe trauma is the major cause for single eye blindness that stem from subsequent proliferative vitreoretinopathy (PVR). Though biomaterials and tissue engineering have significantly advanced drug delivery and management of human diseases, currently there is no effective drug formulation or device to pharmacologically mitigate PVR formation after open-globe eye trauma. This highlighted the challenge we are facing to bring the technology from bench to bedside. The current study reported an engineered episcleral drug film using biodegradable material, Poly(L-lactide)-co-poly(ɛ-caprolactone), and triamcinolone acetonide (TA) as a model drug. The film can be conveniently sized into any shape to fit the configuration of the eye globe trauma and easily installed onto the ruptured sclera during primary trauma repair surgery. The film allows therapeutic TA to slow release for at least 6 months without toxicity and demonstrated a significant benefit to reduce the odds of developing severe PVR by 5.7 times when compared with a no-drug film control on a rabbit trauma PVR model. Our results suggested this micro episcleral drug film as promising drug delivery carrier for the targeted treatment of various unwanted retinal proliferation diseases.